Uric acid is the final product resulting from purine degradation in the liver. The primary route through which uric acid in the body is excreted is the kidney, and about two-thirds of it is excreted in the urine, with the remainder excreted in the stool. Blood uric acid levels are maintained in healthy individuals, but, when an excessive production of uric acid or a decreased excretion of uric acid occurs, this causes hyperuricemia.
Hyperuricemia, in which blood uric acid levels become elevated, is a factor that causes gout and urinary calculus, and furthermore it is said to contribute to nephropathy and arteriosclerosis. In addition, there have recently been an increasing number of reports that the higher the blood uric acid level, the higher the incidence rates of lifestyle-related diseases such as metabolic syndrome and hypertension, chronic kidney disease, and the like, and hyperuricemia is being recognized to be a risk factor for these diseases. Thus, an improvement in hyperuricemia is expected to lead to improvements in various diseases (Non-Patent Document 1).
Recently, the gene (SLC22A12) encoding a human renal urate transporter has been identified. The transporter (urate transporter 1, URAT1) encoded by this gene is a twelve-span transmembrane molecule belonging to the OAT family. Its mRNA is specifically expressed in the kidney, and further, its localization on the apical side of the proximal tubule has been observed in human kidney tissue sections. URAT1-mediated uric acid uptake has been shown by experiments using the Xenopus oocyte expression system. Furthermore, it has been reported that probenecid or benzbromarone, which inhibits URAT1, is useful as a therapeutic or prophylactic agent for hyperuricemia, gout, and the like (Non-Patent Document 2).